Structure of PDB 4xv2 Chain A Binding Site BS01

Receptor Information
>4xv2 Chain A (length=247) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
DWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVPTPQQLQAFKN
EVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHHLHASETKFEM
KKLIDIARQTARGMDYLHAKSIIHRDLKSNNIFLHEDNTVKIGDFGGSIL
WMAPEVIRPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIEMVGRGS
LSPDLSKVRSNCPKRMKRLMAECLKKKRDERPSFPRILAEIEELARE
Ligand information
Ligand IDP06
InChIInChI=1S/C23H20F3N5O2S2/c1-23(2,3)21-30-18(19(34-21)16-10-11-28-22(27)29-16)12-6-4-9-15(17(12)26)31-35(32,33)20-13(24)7-5-8-14(20)25/h4-11,31H,1-3H3,(H2,27,28,29)
InChIKeyBFSMGDJOXZAERB-UHFFFAOYSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(C)(C)c1nc(c(s1)c2ccnc(n2)N)c3cccc(c3F)NS(=O)(=O)c4c(cccc4F)F
ACDLabs 12.01c4(N)nc(c1c(nc(s1)C(C)(C)C)c2c(c(ccc2)NS(=O)(=O)c3c(cccc3F)F)F)ccn4
CACTVS 3.385CC(C)(C)c1sc(c2ccnc(N)n2)c(n1)c3cccc(N[S](=O)(=O)c4c(F)cccc4F)c3F
FormulaC23 H20 F3 N5 O2 S2
NameDabrafenib;
N-{3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide
ChEMBLCHEMBL2028663
DrugBankDB08912
ZINCZINC000068153186
PDB chain4xv2 Chain A Residue 801 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB4xv2 RAF inhibitors that evade paradoxical MAPK pathway activation.
Resolution2.5 Å
Binding residue
(original residue number in PDB)		G464 V471 A481 K483 L505 L514 F516 T529 W531 C532 F583 G593 D594 F595
Binding residue
(residue number reindexed from 1)		G16 V23 A33 K35 L55 L64 F66 T79 W81 C82 F133 G143 D144 F145
Annotation score1
Binding affinityMOAD: ic50=0.00539uM
PDBbind-CN: -logKd/Ki=8.27,IC50=0.0054uM
BindingDB: IC50=1.000000nM,EC50=529nM
Enzymatic activity
Catalytic site (original residue number in PDB) D576 K578 N580 N581 D594 S616
Catalytic site (residue number reindexed from 1) D126 K128 N130 N131 D144 S148
Enzyme Commision number 2.7.11.1: non-specific serine/threonine protein kinase.
Gene Ontology
Molecular Function
GO:0004672 protein kinase activity
GO:0005524 ATP binding
Biological Process
GO:0006468 protein phosphorylation

View graph for
Molecular Function
View graph for
Biological Process
External links
PDB RCSB:4xv2, PDBe:4xv2, PDBj:4xv2
PDBsum4xv2
PubMed26466569
UniProtP15056|BRAF_HUMAN Serine/threonine-protein kinase B-raf (Gene Name=BRAF)

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